Identification of Cellular Binding Sites for a Novel Human Anti-Breast Cancer Peptide
Abstract
We have synthesized a nine amino acid peptide, AFPep, that inhibits the growth of ER+ human breast. Understanding the process by which AFPep mediates its inhibitory activity is extremely important for the development of this drug or other drugs which exploit the same biochemical pathways to arrest breast cancer growth. We have developed and optimized an affinity chromatography procedure to identify the receptor for AFPep by using the peptide as "bait" to isolate proteins from solublized cells which have an affinity for the peptide. A protein of approximately 70 kDa which shows specificity for the linear form of the peptide, AFPep, has been isolated and identified by mass spectroscopy as Hsp72 which together with Hsp9O and other components forms a heterocomplex that binds to the ER and mediates ligand binding and transcriptional activities. The specificity of the interaction between AFPep and Hsp72 and the relevance to the anti-breast cancer activity of AFPep are currently being evaluated. In addition, an in vitro cell culture method which shows consistent inhibition by AFPep of estrogen-stimulated growth of human breast cancer cells has been developed and will be used to evaluate the mechanism of action of the peptide.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425751
Entities
People
- James M Bennett
- Lori Defreest
Organizations
- Albany Medical College